BACKGROUND: Classic risk factors for coronary heart disease (CHD) do not yet predict the majority of new cases. Of the novel risk factors recently explored, elevated depressive symptoms have been found in a number of prospective studies to predict new CHD cases, as have inflammatory markers, including high sensitivity C-Reactive Protein (CRP), interleukin-6 (IL-6), and intercellular adhesion molecule. Interestingly, depression and inflammatory markers have high covariation, and intervention studies indicate that reducing depression may reduce peripheral inflammation, while successfully treating inflammation may ameliorate depressive symptoms. It becomes critical then to know if these candidate CHD risk factors are independent or dependent of the other in the prediction of CHD incidence. SPECIFIC AIMS: To determine if depressive symptoms and inflammatory markers are independent or dependent CHD risk factors, when controlling for the other known CAD risk factors. METHODS: A population-based prospective study (the Nova Scotia Health Survey; NSHS95) was conducted almost 10 years ago, in which participants were randomly selected from the socialized medical registry, which includes all citizens. All classic CHD risk factors were obtained at baseline (age, sex, race, fasting lipids, diabetic status, family CHD history, resting BP, exercise levels, body mass index, smoking status, and socioeconomic status). Depressive symptoms as assessed by the Center for Epidemiological Studies Depression scale were also obtained at baseline. Plasma blood samples were obtained and maintained in a -80 degree (Celsius) freezer. Participants gave permission for medical registry records to be linked to their survey data, so that objectively documented previous and future CAD events could be detected. We propose to assay plasma samples for CRP, IL-6 and ICAM-1 and then to statistically model the associations among depression, inflammation and CHD incidence.